Study of Magrolimab in Combination With Azacitidine Versus Physician's Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Patients With TP53 Mutant Acute Myeloid Leukemia That Have Not Been Treated

Acute Myeloid Leukemia Clinical Trial

— ENHANCE-2  

Official title:

A Phase 3, Randomized, Open-Label Study Evaluating the Safety and Efficacy of Magrolimab in Combination With Azacitidine Versus Physician's Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Previously Untreated Patients With TP53 Mutant Acute Myeloid Leukemia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04778397
• Other study ID #: GS-US-546-5857
• Secondary ID: 2020-003949-11jR
• Status: Terminated
• Phase: Phase 3
• Start date: July 1, 2021
• Est. completion date: March 25, 2024

Study information

• Verified date: April 2024
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical study is to compare the effectiveness of the study drugs, magrolimab in combination with azacitidine, versus venetoclax in combination with azacitidine in participants with previously untreated TP53 mutant acute myeloid leukemia (AML).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 258
• Est. completion date: March 25, 2024
• Est. primary completion date: March 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Individuals with confirmation of acute myeloid leukemia (AML) by World Health Organization criteria, previously untreated for AML, and who have presence of at least 1 TP53 gene mutation that is not benign or likely benign based on evaluation by either central laboratory or an approved local laboratory (after central review of the bone marrow TP53 mitigation next-generation sequencing test results) (individuals with biallelic 17p deletions, loss of both 17p alleles, are eligible based on locally evaluated cytogenetics/karyotype/fluorescence in situ hybridization (FISH) report).
• Individuals with white blood cell (WBC) count = 20×10^3/microliter (µL) prior to randomization. If the individual's WBC is > 20×10^3/µL prior to randomization, the individual can be enrolled, assuming all other eligibility criteria are met. However, the WBC should be = 20×10^3/µL prior to the first dose of study treatment and prior to each magrolimab dose the first 4 weeks (if the individual is randomized to the experimental arm) Note: Individuals can be treated with hydroxyurea and/or leukapheresis throughout the study or prior to randomization to reduce the WBC to = 20×10^3/µL to enable eligibility for study drug dosing.
• The hemoglobin must be = 9 grams per deciliter (g/dL) prior to initial dose of study treatment. Notes: Transfusions are allowed to meet hemoglobin eligibility.
• Individual has provided informed consent.
• Individual is willing and able to comply with clinic visits and procedure outlined in the study protocol.
• Individuals must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, except for individuals less than 75 years of age and appropriate for non-intensive treatment. For these individuals, the ECOG performance status score may be 0 to 3.
• Individuals must have adequate renal function as demonstrated by a creatinine clearance = 30 milliliters per minute calculated by the Cockcroft Gault formula.
• Adequate cardiac function as demonstrated by:
• Lack of symptomatic congestive heart failure and clinically significant cardiac arrhythmias and ischemic heart disease.
• Left ventricular ejection fraction (LVEF) > 50% for individuals appropriate for intensive therapy.
• Adequate liver function as demonstrated by:
• Aspartate aminotransferase = 3.0 × upper limit of normal (ULN).
• Alanine aminotransferase = 3.0 × ULN.
• Total bilirubin = 1.5 × ULN, or primary unconjugated bilirubin = 3.0 × ULN if individual has a documented history of Gilbert's syndrome or genetic equivalent.
• Pretreatment blood cross-match completed.
• Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
• Individuals must be willing to consent to mandatory pretreatment and on-treatment bone marrow biopsies (aspirate and trephines).

Key Exclusion Criteria:

• Positive serum pregnancy test.
• Breastfeeding female.
• Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient.
• Prior treatment with any of the following:
• Cluster of differentiation 47 (CD47) or signal regulatory protein alpha (SIRPa)-targeting agents
• Antileukemic therapy for the treatment of AML (excluding hydroxyurea), hypomethylating agent (HMA), low dose cytarabine and/or venetoclax. Note: Individuals with prior myelodysplastic syndrome (MDS) who have not received prior HMAs or chemotherapeutic agents for MDS are allowed on study. Other prior MDS therapies including, but not limited to, lenalidomide, erythroid stimulating agents, or similar RBC-direct therapies, are allowed. Localized non-central nervous system (CNS) radiotherapy, erythroid and/or myeloid growth factors, hormonal therapy with luteinizing hormone-releasing hormone agonists for prostate cancer, hormonal therapy or maintenance for breast cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand inhibitors are also not criteria for exclusion.
• Individuals who are appropriate for intensive treatment but who have been previously treated with maximum cumulative doses of idarubicin and/or other anthracyclines and anthracenediones will be excluded.
• Individuals receiving any live vaccine within 4 weeks prior to initiation of study treatments.
• For individuals appropriate for intensive therapy, individuals treated with trastuzumab within 7 months prior to initiation of study treatments.
• Current participation in another interventional clinical study.
• Known inherited or acquired bleeding disorders.
• Individuals appropriate for non-intensive therapy, who have received treatment with strong and/or moderate cytochrome P450 enzyme 3A (CYP3A) inducers within 7 days prior to the initiation of study treatments.
• Individuals appropriate for non-intensive therapy who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days prior to the initiation of study treatment.
• Individuals appropriate for non-intensive therapy who have malabsorption syndrome or other conditions that preclude enteral route of administration.
• Clinical suspicion of active CNS involvement with AML.
• Individuals who have acute promyelocytic leukemia.
• Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV.
• Second malignancy, except MDS, treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which individuals are not on active anti-cancer therapies and have had no evidence of active malignancy for at least = 1 year Note: Individuals on maintenance therapy alone who have no evidence of active malignancy for at least = 1 year are eligible.
• Known active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or human immunodeficiency virus (HIV) infection in medical history.
• Active HBV, and/or active HCV, and/or HIV following testing at screening:
• Individuals who test positive for hepatitis B surface antigen (HBsAg). Individuals who test positive for hepatitis B core antibody (anti-HBc) will require HBV deoxyribose nucleic acid (DNA) by quantitative polymerase chain reaction (PCR) for confirmation of active disease.
• Individuals who test positive for HCV antibody. These individuals will require HCV ribose nucleic acid (RNA) quantitative PCR for confirmation of active disease.
• Individuals who test positive for HIV antibody.
• Individuals not currently receiving antiviral therapy and who have an undetectable viral load in the prior 3 months may be eligible for the study. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Magrolimab
Administered intravenously (IV).
• Venetoclax
Administered orally at a dose of 100 milligrams (mg) on Day 1, 200 mg on Day 2, 400 mg on Days 3-28 during Cycle 1, followed by 400 mg on Days 1-28 during every cycle (Cycle=28 days).
• Azacitidine
Administered either subcutaneously (SC) or IV, 75 milligrams per square meter (mg/m^2) on Days 1-7 or Days 1-5, 8 and 9 during every cycle (Cycle=28 days).
• Cytarabine
Induction: administered continuous infusion, 100 or 200 mg/m^2 on Days 1-7 (7+3 induction) and if needed Days 1-5 (5+2 induction) during a cycle (Cycle=Up to 42 Days). Consolidation: administered IV, 1500 or 3000 mg/m^2 on Days 1, 3, and 5 once every 12 hours for up to 4 cycles.
• Daunorubicin
Administered IV peripherally (IVP), 60 mg/m^2 on Days 1-3 (7+3 induction) and if needed Days 1-2 (5+2 induction) during a cycle (Cycle=Up to 42 days).
• Idarubicin
Administered IV, 12 mg/m^2 on Days 1-3 (7+3 induction) and if needed Days 1-2 (5+2 induction) during a cycle (Cycle=Up to 42 days).
• Steroidal Eye Drops
Administered per institutional standard during consolidation.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Canberra Hospital	Garran	Australian Capital Territory
Australia	Andrew Love Cancer Centre, University Hospital Geelong	Geelong	Victoria
Australia	St Vincents Hospital Melbourne	Melbourne	Victoria
Australia	The Alfred	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Calvary Master Newcastle	Waratah	New South Wales
Australia	Westmead Hospital / Department of Haematology and Bone Marrow Transplantation	Westmead	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	Univ. -Klinik für Hämatologie und Internistische Onkologie, Kepler Universitätskilkun GmbHMed	Linz
Austria	Uniklinikum Salzburg, Universitatsklinik f. Innere Medizin III der PMU	Salzburg
Belgium	Algemeen Ziekenhuis Sint-Jan Brugge-Oostende AV	Brugge
Belgium	Universitair Ziekenhuis Brussel	Brussels
Belgium	Grand Hôpital De Charleroi - Notre Dame	Charleroi
Belgium	Universitaire Ziekenhuis Antwerpen	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	AZ Delta vzw	Roeselare
Canada	Tom Baker Cancer Center	Calgary
Canada	Queen Elizabeth II Health Sciences Centre	Halifax
Canada	CIUSSS de L'Est-de-L'Ile-de- Montreal - Hopital Maisonneuve-Rosemont	Montreal
Canada	McGill University Health Centre	Montreal
Canada	Princess Margaret Cancer Centre	Toronto
Canada	Sunnybrook Research Institute	Toronto
Denmark	Aalborg University Hospital	Aalborg
Denmark	Odense University Hospital	Odense C
France	CHU d'Angers	Angers cedex
France	CHU de Caen	Caen cedex
France	CHRU Lille - Hospital Claude Huriez	Lille
France	CHU Limoges	Limoges
France	Central Hospital Lyon Sud	Lyon
France	Institut Paoli Calmettes	Marseille
France	CHU de Nantes, Hotel Dieu	Nantes
France	CHU Nice - Hopital Archet 1	Nice
France	Gustave Roussy	Paris
France	Hopital Haut-Leveque	Pessac
France	IUCT Oncopole	Toulouse
France	Hopitaux de Brabois	Vandoeuvre-lès-Nancy
Germany	Uniklinik RWTH Aachen, Medizinische Klunuk IV - Klinik fur Hamatologie, Onkologie, Hamastaseologie und Srammzelltransplantation	Aachen
Germany	Dept. of Hematology, Oncology and Tumor Immunology, Charite- University Medicine Berlin, Campus Virchow Klinikum	Berlin
Germany	Department of Hematology and Oncology, Braunschweig Community Hospital	Braunschweig
Germany	Universitatsklinikum Carl Gustav Carus Dresden an der Technische Universitat Dresden, Medizinische Klinik und Poliklinik 1, Bereich Hamatologie	Dresden
Germany	Universitätsklinikum Düsseldorf -Klinik für Hämatologie, Onkologie und Klinische Immunologie	Dusseldorf
Germany	Dept. of Medicine II, University Hospital Hamburg-Eppendorf	Hamburg
Germany	Universitatsklinikum Heidelberg, Innere Medizin V, Hamatologie, Onkologie und Rheumatologie	Heidelberg
Germany	Universitatsklinikum Schleswig-Holstein	Kiel
Germany	Universitatsklinikum Koln	Köln
Germany	Klinikum Ludwigshafen Medizinische Klinik A	Ludwigshafen
Germany	Klinikum rechts der Isar der Technischen Universitat Munchen, Klinik und Poliklinik fur Innere Medizin III	Muenchen
Germany	LMU - Klinikum der Universitat Munchen, Medizinische Klinik und Poliklinik III, Campus Grosshadern	München
Germany	Universitatsklinikum Ulm, Zentrum fur Innere Medizin, Innere Medizin III	Ulm
Hong Kong	Prince of Wales Hospital, The Chinese University of Hong Kong	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Italy	Azienda Ospedaliero Universitaria delle Marche	Ancona
Italy	AOU Consorziale Policlinico Bari	Bari
Italy	Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant'Orsola-Malphigi U.O Ematologia	Bologna
Italy	Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRS - Oncologia Medica	Meldola
Italy	Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli U.O.S.C. di Ematologia con Trapianto di Midollo Osseo	Napoli
Italy	SC Ematologia, Azienda Ospedaliera di Perugia - Santa Maria della Misericordia	Perugia
Italy	AORM - AO Riuniti Marche Norde - Pesaro Presidio "San Salvatore" - Muraglia	Pesaro
Italy	Fondazione PTV Policinico Tor Vergata	Roma
Italy	SCDU Ematologia e Terrapie cellulari AO O Ordine Mauriziano Torino	Torino
Italy	ASST Sette Laghi - Ospedale di Circolo e Fondazione Macchi	Varese
Japan	Hyogo Prefectural Amagasaki General Medical Center	Amagasaki
Japan	Chiba Aoba Municipal Hospital	Chiba
Japan	University of Yamanashi Hospital	Chuo-City
Japan	Kyushu University Hospital	Fukuoka
Japan	Fukushima Medical University Hospital	Fukushima-Shi
Japan	Aiiku Hospital	Hokkaido
Japan	Tokai University School of Medicine	Isehara
Japan	Kanazawa University Hospital	Kanazawa
Japan	National Cancer Center Hospital East	Kashiwa
Japan	Hospital of the University of Occupational and Environmental Health, Japan	Kitakyushu-shi
Japan	Kobe City Medical Center General Hospital	Kobe-city
Japan	Gunmaken Saiseikai Maebashi Hospital	Maebashi
Japan	Ehime Prefectural Center Hospital	Matsuyama
Japan	Nagasaki University Hospital	Nagasaki
Japan	Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital	Nagoya
Japan	Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital	Nagoya-Shi
Japan	Okayama University Hospital	Okayama-Shi
Japan	Osaka Metropolitan University Hospital	Osaka-Shi
Japan	Kindai University Hospital	Osakasayama
Japan	National University Corporation Tohoku University Tohoku University Hospital	Sendai
Japan	NTT Medical Center Tokyo	Shinagawa-Ku
Japan	Yamagata University Hospital	Yamagata
Japan	University of Fukui Hospital	Yoshida-gun
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital del la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Institut Catala d'Oncologia	Barcelona
Spain	Complejo Asistencial Universitario de Burgos/H.U. de Burgos	Burgos
Spain	Complejo Hospitalario San Pedro de Alcantara	Cáceres
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Hospital Universitario de Gran Canaria Doctor Negrin	Las Palmas de Gran Canaria
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario de La Princesa	Madrid
Spain	MD Anderson Cancer Center Madrid	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Clinica Universidad de Navarra - Pamplona (Main Site)	Pamplona
Spain	Complejo Asistencial Universitario de Salamanca - Hsopital Clinico	Salamanca
Spain	Hospital U. Marques de Valdecilla	Santander
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitari I Politècnic La Fe	Valencia
Sweden	Universitetssjukhus, Hematologimottagnungen	Lund
Switzerland	Universitatsspital Basel - Klinik fur Hamatrologie, Bereich Innere Medizin	Basel
Switzerland	Inselspital, Universitatsspital Bern - Universitatsklinik fur Medizinisch Onkologie	Berne
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	United Lincolnshire Hospitals NHS Trust, Pilgrim Hospital, Sibsey Road	Boston
United Kingdom	Cambridge University Hospital NHS Foundation Trust	Cambridge
United Kingdom	Cardiff and Vale University Health Board	Cardiff Wales
United Kingdom	Barts Health NHS Trust	City of London
United Kingdom	NHS Tayside	Dundee
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	King's College NHS Foundation Trust	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	Oxford University Hospital NHS Foundation Trust	Oxford
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton
United Kingdom	The Christie NHS Foundation Trust	Withington
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	UNC Hospitals, The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern Memorial Hospital/Main Lab	Chicago	Illinois
United States	The University of Chicago Medical Centre	Chicago	Illinois
United States	The Ohio State University Wexner Medical Center/ James Cancer Hospital	Columbus	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	City of Hope (City of Hope National Medical Center, City of Hope Medical Center)	Duarte	California
United States	Duke Blood Cancer Center	Durham	North Carolina
United States	University of Kansas Hospital	Fairway	Kansas
United States	Prisma Health Cancer Institute	Greenville	South Carolina
United States	St. Francis Cancer Center	Greenville	South Carolina
United States	Baylor College of Medicine Medical Center	Houston	Texas
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	MidAmerica Division, Inc., c/o Research Medical Center	Kansas City	Missouri
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	USC/ Norris Comprehensive Cancer Center	Los Angeles	California
United States	Miami Cancer Institute	Miami	Florida
United States	Froedtert Hospital / Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Tulane Medical center	New Orleans	Louisiana
United States	Columbia University Medical Center - Herbert Irving Pavilion	New York	New York
United States	University of Oklahoma Health Sciences Center - OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	UC Irvine Health	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
United States	Memorial Cancer Institute	Pembroke Pines	Florida
United States	Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization	Philadelphia	Pennsylvania
United States	Mayo Clinic Cancer Center Outpatient Pharmacy	Rochester	Minnesota
United States	SSM Health Saint Louis University Hospital	Saint Louis	Missouri
United States	Huntsman Cancer Institute ,The University of Utah	Salt Lake City	Utah
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Denmark,  France,  Germany,  Hong Kong,  Italy,  Japan,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) in Participants Appropriate for Non-intensive Therapy	The OS is measured from the date of randomization to the date of death from any cause. Those whose deaths are not observed during the study will be censored at their last known alive date.	Randomization up to death or end of study (up to 27 months) whichever occurs first
Secondary	Overall Survival in All Participants	The OS is measured from the date of randomization to the date of death from any cause. Those whose deaths are not observed during the study will be censored at their last known alive date.	Randomization up to death or end of study (up to 27 months) whichever occurs first
Secondary	Event-Free Survival (EFS) in All Participants	The EFS is defined as time from the date of randomization to the earliest date of documented relapse from complete remission (CR), treatment failure (defined as failure to achieve CR within 6 months of treatment with magrolimab + azacitidine or venetoclax + azacitidine, or up to 2 months of treatment with 7 + 3 chemotherapy), or death from any cause. Response assessments or death post SCT or new anti-AML therapies will be included. Those who are not observed to have one of these events during the study will be censored at the date of their last response assessment with clear documentation of no relapse during the study. The date of randomization will be assigned as the event date for participants with treatment failure.	Randomization up to end of study (up to 27 months)
Secondary	Rate of Complete Remission (CR) in All Participants	The rate of CR is the percentage of participants who achieve a CR, including CR without minimal residual disease (CR MRD-) and CR with positive or unknown minimal residual disease (CR MRD+/unk) within 6 months of treatment with magrolimab + azacitidine or venetoclax + azacitidine, or within 2 months of treatment with 7 + 3 chemotherapy, as defined by investigators based on European Leukemia Net (ELN) 2017 AML (ELN 2017 AML) with modifications, while on study prior to initiation of any new anti-AML therapy or stem cell transplant (SCT).	6 months for the Magrolimab + Azacitidine; Control Arm: Venetoclax + Azacitidine arm, and 2 months for Control Arm: 7+3 Chemotherapy
Secondary	Rate of CR Without Minimal Residual Disease (CR MRD-) in All Participants	The rate of CR MRD- is the percentage of participants who achieve a CR MRD- within 6 months treatment with magrolimab + azacitidine or venetoclax + azacitidine, or within 2 months of treatment with 7 + 3 chemotherapy, as defined by investigators based on ELN 2017 AML with modifications, while on study prior to initiation of any new anti-AML therapy or SCT.	6 months for the Magrolimab + Azacitidine; Control Arm: Venetoclax + Azacitidine arm, and 2 months for Control Arm: 7+3 Chemotherapy
Secondary	Rate of CR and Complete Remission with Partial Hematologic Recovery (CR+CRh) in All Participants	The CR+CRh rate is the percentage of participants who achieve a CR (including CR MRD- and CR MRD+/unk) or CRh as defined by CR with partial platelet and absolute neutrophil count (ANC) recovery while on study prior to initiation of any new anti-AML therapy or SCT.	6 months for the Magrolimab + Azacitidine; Control Arm: Venetoclax + Azacitidine arm, and 2 months for Control Arm: 7+3 Chemotherapy
Secondary	Duration of Complete Remission (DCR)	The DCR is measured from the time the assessment criteria are first met for CR (including CR MRD- and CR MRD+/unk) within 6 months of treatment with magrolimab + azacitidine or venetoclax + azacitidine, or within 2 months of treatment with 7 + 3 chemotherapy, until the first date of AML relapse or death (including assessments post SCT). Those who are not observed to have relapsed disease or death while on study will be censored at the date of their last response assessment with no evidence of relapse. If participants start taking new anti-AML therapies (excluding maintenance therapy) before relapse, the DCR will be censored at the last response assessment before the initiation of the new anti-AML therapies.	First CR achieved within 6 months for the Magrolimab + Azacitidine; Control Arm: Venetoclax + Azacitidine arm, and 2 months for Control Arm: 7+3 Chemotherapy up to the end of study (up to 27 months)
Secondary	Duration of CR+CRh	The duration of CR+CRh is measured from the time the assessment criteria are first met for CR (including CR MRD- and CR MRD+/unk) or CRh within 6 months of treatment with magrolimab + azacitidine or venetoclax + azacitidine, or within 2 months of treatment with 7 + 3 chemotherapy, until the first date of AML relapse or death (including assessments post SCT). Those who are not observed to have relapsed disease or death while on study will be censored at the date of their last response assessment with no evidence of relapse. If patients start taking new anti-AML therapies (excluding maintenance therapy) before relapse, the duration of CR + CRh will be censored at the last response assessment before the initiation of the new anti-AML therapies.	First CR or CRh achieved within 6 months for the Magrolimab + Azacitidine; Control Arm: Venetoclax + Azacitidine arm, and 2 months for Control Arm: 7+3 Chemotherapy up to the end of study (up to 27 months)
Secondary	Percentage of Participants Experiencing Grade = 3 Treatment-Emergent Adverse Events (TEAEs) According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0		First dose date up to last dose date (Maximum: 24 months) plus 70 days
Secondary	Percentage of Participants Experiencing Grade = 3 Treatment-Emergent Laboratory Abnormalities According to the NCI CTCAE Version 5.0		First dose date up to last dose date (Maximum: 24 months) plus 70 days
Secondary	Serum Concentration of Magrolimab		Within 72 hours predose on Day 1 of Cycle 1, within 12 hours predose on Day 8 of Cycle 1 and Day 1 of Cycles 2, 3, 5, 7, 10, 13, and end of treatment (EOT) EOT=Maximum: 24 months (Cycle=28 days)
Secondary	Rate of Anti-Magrolimab Antibody Incidence	Rate of anti-magrolimab antibody incidence is defined as the percentage of participants with anti-magrolimab antibodies.	Within 72 hours predose on Day 1 of Cycle 1, within 12 hours predose on Day 1 of Cycles 2, 3, 5, 7, 10, 13 and end of treatment (EOT) EOT=Maximum: 24 months (Cycle=28 days)

External Links

•   Gilead Clinical Trials Website